Figure 6.

Effect of TIGIT blockade on HIV‐1‐specific NK cell and CD8⁺ T‐cell activation and elimination of endogenously infected PVR‐expressing CD4⁺ T cells ex vivo. (a) PBMC from PLWH were depleted of CD8⁺ T cells, treated with IL‐2 and assessed for HIV‐1 infection by p24 expression. Representative plots depict initial gating on CD3⁺CD4⁺CD8^dep lymphocytes and determination of the percentage of PVR expression for (b) p24⁺ or (c) p24^‐ cells. (d) Summary data as in a–c from 10 individuals. The left axis depicts percentage of CD4⁺ T cells that were p24⁺ 72–144 h after CD8⁺ T‐cell depletion, and the right axis represents the percentage of PVR expressing cells in either the p24⁺ or p24⁻ CD4⁺ T‐cell populations. ANOVA with Tukey's multiple comparison ***P = 0.0001. Error bars in d represent median with IQR. Following 72 h PHA‐P activation of PBMC, (e, f) loss of p24⁺PVR⁺CD4⁺ T cells or (g, h) NK cell and (i, j) CD8⁺ T‐cell degranulation was evaluated 24 h after treatment with either IgG₁ or anti‐TIGIT mAb in the presence of anti‐HIV‐1 antibodies. Histogram plots for each analysis are depicted in e, g, i with data summarised for 10 participants in f, h, j. Degranulation was assessed after gating on lymphocytes and enumerating CD107a‐expressing cells in either CD3^‐CD56⁺ (NK cell) or CD3⁺CD8⁺ (CD8⁺ T cell) populations. P‐values in f, h, j were calculated using the Student's paired t‐test **P = 0.0034 ***P = 0.0007.